| RRC ID |
44726
|
| 著者 |
Kubo S, Takagi-Kimura M, Logg CR, Kasahara N.
|
| タイトル |
Highly efficient tumor transduction and antitumor efficacy in experimental human malignant mesothelioma using replicating gibbon ape leukemia virus.
|
| ジャーナル |
Cancer Gene Ther
|
| Abstract |
Retroviral replicating vectors (RRVs) have been shown to achieve efficient tumor transduction and enhanced therapeutic benefit in a wide variety of cancer models. Here we evaluated two different RRVs derived from amphotropic murine leukemia virus (AMLV) and gibbon ape leukemia virus (GALV), in human malignant mesothelioma cells. In vitro, both RRVs expressing the green fluorescent protein gene efficiently replicated in most mesothelioma cell lines tested, but not in normal mesothelial cells. Notably, in ACC-MESO-1 mesothelioma cells that were not permissive for AMLV-RRV, the GALV-RRV could spread efficiently in culture and in mice with subcutaneous xenografts by in vivo fluorescence imaging. Next, GALV-RRV expressing the cytosine deaminase prodrug activator gene showed efficient killing of ACC-MESO-1 cells in a prodrug 5-fluorocytosine dose-dependent manner, compared with AMLV-RRV. GALV-RRV-mediated prodrug activator gene therapy achieved significant inhibition of subcutaneous ACC-MESO-1 tumor growth in nude mice. Quantitative reverse transcription PCR demonstrated that ACC-MESO-1 cells express higher PiT-1 (GALV receptor) and lower PiT-2 (AMLV receptor) compared with normal mesothelial cells and other mesothelioma cells, presumably accounting for the distinctive finding that GALV-RRV replicates much more robustly than AMLV-RRV in these cells. These data indicate the potential utility of GALV-RRV-mediated prodrug activator gene therapy in the treatment of mesothelioma.
|
| 巻・号 |
20(12)
|
| ページ |
671-7
|
| 公開日 |
2013-12-1
|
| DOI |
10.1038/cgt.2013.67
|
| PII |
cgt201367
|
| PMID |
24201868
|
| PMC |
PMC8185610
|
| MeSH |
Animals
Cell Line, Tumor
Cytosine Deaminase / genetics
Cytosine Deaminase / metabolism
Disease Models, Animal
Female
Gene Expression
Gene Order
Genetic Therapy
Genetic Vectors / administration & dosage
Genetic Vectors / genetics*
Humans
Leukemia Virus, Gibbon Ape / genetics*
Lung Neoplasms / genetics*
Lung Neoplasms / metabolism
Mesothelioma / genetics*
Mesothelioma / metabolism
Mesothelioma, Malignant
Mice
Prodrugs
Transduction, Genetic*
Virus Replication
Xenograft Model Antitumor Assays
|
| IF |
4.534
|
| 引用数 |
10
|
|
WOS 分野
|
MEDICINE, RESEARCH & EXPERIMENTAL
BIOTECHNOLOGY & APPLIED MICROBIOLOGY
GENETICS & HEREDITY
ONCOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
ACC-MESO-1(RCB2292) |
